EPA/600/8-88/013
                                            July, 1987
          HEALTH EFFECTS ASSESSMENT
                FOR ACROLEIN
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
      OFFICE OF  RESEARCH AND  DEVELOPMENT
    U.S. ENVIRONMENTAL PROTECTION AGENCY
            CINCINNATI, OH 45268

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                                  DISCLAIMER
  *

    This   document   has   been  reviewed   1n   accordance   with   the   U.S.
Environmental  Protection  Agency's  peer and  administrative  review policies
and approved for publication.  Mention  of  trade  names  or commercial products
does not constitute endorsement or recommendation for use.
                                      11

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                                    PREFACE
   •

    This,  report  summarizes and evaluates Information  relevant  to a prelimi-
nary  Interim  assessment of adverse health  effects  associated  with acroleln.
All  estimates  of  acceptable  Intakes  and  carcinogenic potency  presented  In
this  document  should  be  considered  as  preliminary reflecting  limited  re-
sources allocated  to this project.   Pertinent  toxlcologlc  and environmental
data were  located  through  on  line  literature searches of the TOXLINE and the
CHEMFATE/DATALOG data  bases.   The basic  literature searched supporting this
document  Is current  up to May, 1986.   Secondary  sources  of Information have
also been  relied  upon  In  the preparation of this report and represent large
scale  health  assessment  efforts   that  entail   extensive   peer  and  Agency
review.   The  following Office of Health  and Environmental  Assessment (OHEA)
sources have been extensively utilized:

    U.S.  EPA.   1980a.    Ambient  Water  Quality  Criteria  for Acrolelns.
    Prepared  by   the  Office  of  Health  and Environmental  Assessment,
    Environmental  Criteria and  Assessment   Office,  Cincinnati,  OH for
    the Office of  Water  Regulations  and Standards,  Washington, DC.  EPA
    440/5-80-016.  NTIS PB81-117277.

    U.S.  EPA.    1985a.   Health  and   Environmental  Effects   Profile for
    Acroleln.    Prepared  by   the  Office of Health and  Environmental
    Assessment,  Environmental  Criteria  and Assessment  Office,  Cincin-
    nati,  OH  for  the   Office  of  Solid Waste  and  Emergency  Response,
    Washington, DC.

    U.S.   EPA.    1986a.    Health  Assessment   Document   for  Acroleln.
    Prepared  by   the  Office  of  Health  and Environmental  Assessment,
    Environmental  Criteria  and  Assessment  Office, Research  Triangle
    Park,  NC  for  the   Office  of  Air  Quality  Planning  and Standards,
    Washington, DC.  EPA 600/8-86-OHA.

    The Intent In  these assessments  1s  to suggest acceptable exposure levels
for  noncarclnogens  and   risk   cancer   potency  estimates   for  carcinogens
whenever  sufficient  data  were  available.  Values were not  derived  or larger
uncertainty factors  were  employed  when  the variable data  were  limited  In
scope  tending   to  generate  conservative   (I.e.,   protective)  estimates.
Nevertheless,   the  Interim values  presented  reflect the relative  degree  of
hazard or risk associated with exposure to the chemical(s) addressed.

    Whenever  possible, two  categories  of   values   have  been   estimated  for
systemic  toxicants  (toxicants  for  which  cancer  Is  not   the  endpolnt  of
concern).  The first,  RfD$ (formerly  AIS)  or subchronlc reference dose,  Is
an estimate of an  exposure level that would .not be expected to cause adverse
effects when  exposure  occurs  during  a  limited  time Interval   (I.e.,  for  an
Interval  that  does  not  constitute  a  significant  portion of  the Hfespan).
This type  of exposure  estimate has not  been extensively  used, or rigorously
defined,  as  previous  risk assessment  efforts  have been primarily directed
towards exposures  from  toxicants  In  ambient  air   or  water  where lifetime
exposure   1s  assumed.   Animal  data  used  for   RFD$  estimates  generally
Include exposures  with durations of  30-90  days.   Subchronlc  human  data  are
                                      111

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rarely available.   Reported  exposures are usually  from  chronic  occupational
exposure  situations or  from reports  of acute  accidental  exposure.   These
values  are   developed  for  both   Inhalation  (RfD$j)   and  oral   (RfD$o)
exposures.

    The  RfO   (formerly  AIC)  Is   similar  In  concept and  addresses  chronic
exposure.  It Is an estimate of  an  exposure  level  that would not be expected
to cause  adverse effects when exposure  occurs for  a significant  portion  of
the Hfespan  [see  U.S. EPA  (1980b)  for  a discussion of this  concept].   The
RfO  Is route-specific  and  estimates acceptable  exposure  for  either  oral
(RfDg)  or  Inhalation   (RfDj)  with  the  Implicit   assumption  that  exposure
by other routes Is Insignificant.

    Composite  scores   (CSs)  for  noncarclnogens  have also  been  calculated
where  data  permitted.   These  values are  used  for Identifying  reportable
quantities and  the methodology  for  their development  Is  explained  "in  U.S.
EPA (1983).

    For compounds  for  which there Is  sufficient evidence  of carclnogenlclty
RfD$  and  RfD values are not derived.   For  a discussion of  risk  assessment
methodology  for  carcinogens refer  to U.S.  EPA  (1980b).   Since cancer  Is  a
process that  Is  not characterized  by a  threshold,  any  exposure contributes
an Increment  of  risk.   For  carcinogens,  q-|*s have  been computed,  1f appro-
priate, based on oral  and Inhalation data If available.
                                      1v

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                                   ABSTRACT
    In  order  to  place  the  risk  assessment  evaluation  In  proper  context,
refer  to  the preface  of  this  document.  The  preface outlines  limitations
applicable to all documents of  this  series as well  as the appropriate Inter-
pretation and use of the quantitative estimates  presented.

    The unpublished study  by  Ujlnsky (n.d.)  Indicates that acroleln  may be
carcinogenic  following  oral  exposure.   Using   the  significantly  Increased
Incidence of adrenal cortical  adenomas In female rats  found  1n the LlJInksy
(n.d.)  study,  a  human   q-|*   of   0.17   (mg/kg/day)'1  was   derived.    Data
Indicating a  carcinogenic  effect  of acroleln following  Inhalation exposure
were not available,  so  an Inhalation q-|* could not be derived.

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                               ACKNOWLEDGEMENTS
  *

    The  Initial  draft  of  this  report  was  prepared  by  Syracuse  Research
Corporation  under  Contract No.  68-03-3112  for  EPA's  Environmental  Criteria
and  Assessment  Office,  Cincinnati,  OH.   Dr.  Christopher  DeRosa and  Karen
Blackburn  were  the  Technical   Project  Monitors  and  John  Helms  (Office  of
Toxic  Substances)  was  the Project  Officer.   The final  documents   In  this
series  were prepared  for  the  Office  of  Emergency  and Remedial  Response,
Washington, DC.

    Scientists from  the following U.S. EPA  offices provided  review  comments
for this document series:

         Environmental Criteria and Assessment Office, Cincinnati, OH
         Carcinogen Assessment Group
         Office of A1r Quality Planning and Standards
         Office of Solid Haste
         Office of Toxic Substances
         Office of Drinking Water

Editorial review for the document series was provided  by the following:

    Judith Olsen and Erma Durden
    Environmental Criteria and Assessment Office
    Cincinnati,  OH

Technical  support  services  for  the  document   series  was  provided  by  the
following:

    Bette Zwayer, Jacky Bohanon and K1m Davidson
    Environmental Criteria and Assessment Office
    Cincinnati,  OH
                                      v1

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TABLE OF CONTENTS

1.
2.


3.










4.






5.
6.




ENVIRONMENTAL CHEMISTRY AND FATE 	
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL 	
2.2. INHALATION 	 ' 	
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 	
3.1. SUBCHRONIC 	
3.1.1. Oral 	
3.1.2. Inhalation 	
3.2. CHRONIC 	
3.2.1. Oral 	
3.2.2. Inhalation 	
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral 	
3.3.2. Inhalation 	
3.4. TOXICANT INTERACTIONS 	
CARCINOGENICITY 	
4.1. HUMAN DATA 	
4.2. BIOASSAYS 	
4.2.1. Oral 	
4.2.2. Inhalation 	
4.3. OTHER RELEVANT DATA 	
4.4. HEIGHT OF EVIDENCE 	
REGULATORY STANDARDS AND CRITERIA 	
RISK ASSESSMENT 	
6.1. SUBCHRONIC REFERENCE DOSE (RfDs) 	
6.1.1. Oral (RfOso) 	
6.1.2. Inhalation (RfDsi) 	
Paqe
... 1
... 3
... 3
... 3
... 4
... 4
... 4
... 4
. . . 10
. . . 10
. . . 10
, , , 11
. . . 11
. . . 11
. . . 11
. . . 13
. . . 13
. . . 13
. . . 13
13
. . . 14
. . . 16
. . . 18
. . . 20
20
. . . 20
. . . 20

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                             TABLE  OF  CONTENTS
    6.2.   REFERENCE DOSE (RfD)
           6.2.1.   Oral (Rf00)	   20
           6.2.2.   Inhalation (RfDj) 	   20

    6.3.   CARCINOGENIC POTENCY (q^) .  .	   20

           6.3.1.   Oral.	   20
           6.3.2.   Inhalation. ....  	   21

7.  REFERENCES	   22

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                             LIST OF  ABBREVIATIONS
CAS                     Chemical Abstract Service
CBI                     Confidential business Information
CS                      Composite score
DMSO                    Dimethyl sulfoxlde
DNA                     Oeoxyrlbonuclelc acid
1050                    Oose lethal to 50% of recipients
LOAEL                   Lowest-observed-adverse-effect level
MED                     Minimum effective dose
NOEL                    No-observed-effect level
PEL                     Permissible exposure limit
ppm                     Parts per million
RD5Q                    Dose at which respiratory rate 1s decreased 50%
RfD                     Reference dose
RfDj                    Inhalation reference dose
RfDg                    Oral reference dose
RfD$                    Subchronlc reference dose
                        Subchronlc Inhalation reference dose
                        Subchronlc oral reference dose
RV(j                     Dose-rating value
RVe                     Effect-rating value
STEL                    Short-term effect level
TLV                     Threshold limit value
TWA                     Time-weighted average
                                      1x

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                     1.  ENVIRONMENTAL CHEMISTRY AND FATE

    Selected  physical   and  chemical  properties  and  environmental  fate  of
acroleln are listed 1n Table 1-1.
    Acroleln 'exposed to  sunlit  atmospheres  Is  decomposed rapidly by reaction
with  photochemically  generated  hydroxyl  radicals  (estimated  half-lives  of
0.23-0.42  days).    Products  of  the  reaction  of  acroleln  with OH  radical
Include  CO,  formaldehyde,  glycoaldehyde,  and,  1n  the presence  of  nitrogen
oxides, peroxynHrates and  nitric add.   Reaction  of  acroleln with  ozone may
also  contribute  to the  atmospheric  depletion  of  acroleln  (estimated  half-
life  of  2 days).   The  presence of  acroleln  In rainwater  samples  suggests
that wet deposition may  contribute  to the removal  of  acroleln from air  (U.S.
EPA,  1985a).   In  aquatic  media,   acroleln  apparently  undergoes rapid  but
reversible  hydratlon   to  product   p-hydroxyprop1onaldehyde.    Removal   by
blodegradatlon and  volatilization  may a.lso  be significant.   Based  on  water
solubility  and  the octanol/water  partition  coefficient,  acroleln  1s  not
expected to bloaccumulate In aquatic organisms; however,  the experimentally
determined  maximum  bloconcentratlon  factor  of  344  1n  blueglll  sunflsh
Indicates  potential for  moderate  bloaccumulatlon  (U.S.  EPA,  1985a).   The
half-life of acroleln In  soil systems could  not  be located 1n the literature
searched.  The  estimated soil  adsorption coefficients  of  5 and 32  suggest
that  acroleln  1s readily susceptible to  leaching  (U.S.  EPA,  1985a).   The
relatively high vapor pressure  of  acroleln (220 mm Hg at  20°C;  269  mm  Ho at
2S°C) suggests that It may volatilize rapidly from dry soil surfaces.
0103h                               -1-                              10/23/86

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                                  TABLE  1-1

     Selected  Physical  and  Chemical  Properties and Half-Lives  for Acroleln
          Property
        Value
   Reference
CAS number:

Chemical class:

Molecular weight:

Vapor pressure:



Water solubility:
Log octanol/water
  partition coefficient:
Bloconcentratlon factor
Soil adsorption coefficient:

Half-lives 1n
  Air:
  Water:
107-02-8

unsaturated aldehyde

56.06

220 mm Hg (20°C)
269 mm Hg (2S°C)
330 mm Hg (30°C)

2.00xlO» to 2.08xlO»
mg/l (20°C)
4.00xlO~» mg/l (25°C)


-0.01
<344, blueglll
Tlepomls macrochlrus)
0.6-0.23 (estimated)

5-32 (estimated)
<1 day (estimated)
<1 day - 3 days
U.S. EPA. 1985a
U.S. EPA, 1985a
Hansch and Leo.
1985
U.S. EPA. 1985a

U.S. EPA, 1985a
U.S. EPA, 1985a
U.S.. EPA, 1985a
0103h
  -2-
       10/23/86

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           2.   ABSORPTION FACTORS  IN  HUMANS  AND  EXPERIMENTAL ANIMALS
  f
2.1.   ORAL
    Dramlnskl  et  al. (1983)  Indicated  that acroleln  Is  at  least  partially
absorbed following oral  exposure.  In this  study,  the  metabolites s-carboxy-
ethylmercapturlc acid  or s- (proplonlc acid  methyl ester) mercapturlc  add
(or both  In  combination)  were detected  In the urine  of rats  orally  dosed
with  acroleln at  10 mg/kg.   The  quantity of  metabolite recovered was  not
reported.
    Brabec  (1982)  stated  that the  extremely  reactive acroleln  reacts  with
epithelial  surfaces,  tending  to  prevent  passage  of  acroleln  Into  the
Interior  of  the   body.   Further  Information  regarding   the absorption  of
acroleln  following  oral  exposure  could  not  be  located  In the  available
literature.
2.2.   INHALATION
    The only  study available concerning the absorption of acroleln following
Inhalation  exposure  was  conducted by Egle  (1972).   In this  study,  anesthe-
tized mongrel dogs were  exposed to acroleln at  air  concentrations of 0.4-0.6
mg/i  (400-600 mg/m3)  for  1-3 minutes.   Of  the   Inhaled  acroleln,  81-84%
was retained.  Egle  (1972)  also examined  retention of  acroleln  In the  upper
respiratory  tract  In dogs  In  which  the  trachea was  severed just  above  the
bifurcation.  Only -20%  of the Inhaled acroleln  reached the  lower  respira-
tory  tract,  as   retention  In the  upper  tract  removed  -80%  of  Inhaled
acroleln.   Retention In the lower  tract  was -70%.
0103h                                3-                              01/13/87

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                3.   TOXICITY  IN  HUMANS AND  EXPERIMENTAL ANIMALS
3.1.   SUBCHRONIC
3.1.1.   Oral.  Only  limited data concerning the  toxic  effects  of  acroleln
following subchronlc  oral exposure were  available.   Albln  (1962)  (summarized
1n  U.S.  EPA,  1980a),  provided  rats  with drinking water containing  acroleln
at  concentrations  <200 mg/i  for  90 days.   The only  effect  observed was  a
slight weight  reduction at  200 mg/1 acroleln.   This  effect was  attributed
to the unpalatablllty of the water,  which decreased water Intake.
    In a  similar  study by  Newell (1958)  (reviewed  by  NAS,  1977),  acroleln
was  added  to  drinking water  1n concentrations  of 5,  13,  32,  80  and  200
mg/i  and  given to  rats for  90  days.   No effects  on  hematologlcal  param-
eters, organ  weights  or pathology  (not  otherwise specified) were  observed.
The only effect noted was a  decrease In  water  consumption  during the first 3
weeks  of  the  study.   In  a  second  study  (Newell,  1958),  male rats  were
provided with  drinking water  containing  600,   1200  or 1800 mg  acroleln/i
for  60 days.   At   1200  and  1800 mg/l,  all  rats  died from lack  of  water
Intake.  At 600 mg/t, 1/5  rats died.   No other  effects  were reported.
3.1.2.   Inhalation.  Studies of  the toxic effects of  subchronlc  Inhalation
exposure to  acroleln Indicate  that  Inhalation  exposure to  acroleln results
In  morphological  changes  1n the  respiratory   system,  especially  the  upper
dlrways.  A  few  representative  studies  conducted at  concentrations at  or
rear  LOAELs  will  be  presented  In this  section.  More  complete  reviews  are
f-vallable In Carson et al.  (1981) and Beauchamp et al.  (1985).
    Lyon et al. (1970)  exposed  groups of 7 male and 7  female NMRI:0 Sprague-
Oawley rats, similar  numbers  of  Princeton  or Hartly  guinea pigs,  groups of 9
male  squirrel  monkeys  and  groups of 2  male beagle dogs   to acroleln.   The
0103H                               -4-                              10/23/86

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exposure  regimens  used were  acroleln vapor  at  0.7 or  3.7  ppm  {1.6  or  8.5
mg/m3)  for 8  hours/day,   5  days/week  for  6  weeks,  or  continuous  exposure
for  90 days  at  0.22,  1.0 or  1.8  ppm  (0.50,  2.3 or  4.1  mg/m3).   Similar
groups  of  each   species   were  maintained  as  controls.   Body  weights  and
hematologlcal  determinations   were   recorded  before   and  after  exposure.
Immediately  before termination  of   the  study,  serum  alanlne and  aspartate
amlnotransferase activities  and blood urea nitrogen  levels  were determined.
Hlstopathologlcal  examination of  the  lungs, heart,  liver, spleen and kidneys
was done on all dogs and monkeys and on half of the guinea pigs and rats.
    Observation of  the exposed animals  revealed  no signs of  toxlclty after
repeated  exposures  at 0.7 ppm.   Hlstologlcal  examination of  the  lungs  from
all  species  exposed repeatedly at 0.7  ppm showed  mild  chronic  Inflammatory
changes and  occasional mild emphysema.  Inflammatory changes  In the bronchi
were more pronounced In monkeys and dogs.
    Dogs  and  monkeys   exposed  repeatedly to  acroleln  at 3.7  ppm  showed  eye
Irritation,  excessive  salivation  and  labored breathing.   After the  first
week of exposure,  these signs were  less  severe,  although eye  Irritation per-
sisted throughout  the  study (Lyon et al.,  1970).   At  this exposure  regimen,
two  monkeys  died;   both had pulmonary  lesions.   Rats  exposed repeatedly  at
3.7  ppm  had  significantly reduced weight  gain.   No other  signs of  toxlclty
were  observed  In  rats or guinea pigs.   No  effects  on  hematology  or  blood
chemistry were observed 1n any  species.   Nonspecific  Inflammatory hlstologlc
changes were  found In  the lungs, liver  and  kidneys of  all  species  at  3.7
ppm.   Squamous cell metaplasia and  basal  cell hyperplasla  were observed  In
the  tracheas of  dogs  and  monkeys.  Necrotlzlng bronchitis  and squamous  cell
metaplasia of the lungs were found 1n 7/9 monkeys.
0103h                               -5-                              01/13/87

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    Observation  of  animals  exposed  at  0.22 ppm  continuously  for  90  days
revealed no  toxic effects.   H1stolog1c  changes  at 0.22 ppm  paralleled  those
at  the 0.7  ppm repeated  exposure.   In  addition,  at  0.22  ppm  nonspecific
Inflammatory changes were observed In liver,  lung, kidney  and  heart  sections
from monkeys,  guinea  pigs  and dogs.  Dogs  and  monkeys exposed  continuously
at  1.0  and  1.8  ppm showed severe Irritation as  described for  the  repeated
exposure study.   At 1.0 and  1.8 ppm,  rats  had  decreased body  weight  gains
compared with  controls.  Guinea  pigs  exposed continuously at  1.0  ppm  showed
pulmonary  Inflammation  and  occasional  foci   of  liver  necrosis.  At  1.0  ppm,
3/9 rats examined  h1stolog1cally had foci  of liver  necrosis  and  occasional
pulmonary  hemorrhages.   Dogs  at  this  exposure  level had  Inflamed  lungs,
liver and  kidneys.   At 1.8 ppm,  all  animals examined  hlstologlcally  showed
Inflammatory changes  In  the  lungs,  liver, kidneys,  brain  and  heart.   H1sto-
loglcal changes  In the  lungs and  bronchi   paralleled  those  observed  after
repeated exposure at 3.7 ppm acroleln (Lyon  et al.,  1970).
    Another  study  that examined  the  effects of subchronlc  Inhalation  expo-
sure to  acroleln In  several  species was conducted  by Feron  et al.  (1978).
Groups  of  20 Syrian golden hamsters, 12  SPF  Wlstar  rats and 4 Dutch rabbits
of  each  sex were exposed  to acroleln  vapor at  0,  0.4,  1.4 or 4.9 ppm (0,
0.9. 3.2   or 11.2  mg/m3),  6  hours/day,  5  days/week  for  13 weeks.   Food
consumption  and body  weights were  measured weekly.   Hematology,  clinical
chemistry  and  ur1na!ys1s determinations  were made  at 12 weeks.    At  study
termination,  necropsies were  performed,  organ  weights   were recorded  and
hlstopathologlcal examinations of major organs and tissues were performed on
all control  and high-dose animals.   The respiratory  tracts  of all  animals
were examined hlstopathologlcally.
0103h                               -6-                              10/23/86

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  •  At  0.4 ppm,  no toxic  signs  were  noted  In  any  species.   Rabbits  were
sneezing and  rats  and  hamsters appeared narcotized at  1.4 ppm.   At 4.9 ppm.
Increased  salivation and nasal secretion,  and  eye Irritation were  noted  In
all species.   At  the highest dose, 3/12 male and 3/12  female rats died; one
hamster  was  sacrificed  at  week  12  when  moribund  with  renal  failure.
Decreased  weight  gain  was  observed 1n rats and  rabbits exposed  at  1.4 and
4.9 ppm and In hamsters at 1.4 ppm.
    No  effects  on  hematologlcal  or  clinical  chemistry  parameters  were
observed In any species  at  any exposure concentration.   At 4.9 ppm, relative
weights of  lungs  In all  three species, of  the  heart  and kidneys 1n hamsters
and rats, and of adrenals 1n rats were Increased compared with controls.
    At  the highest  exposure concentration, marked  hlstologlc  changes  were
observed In the epithelium of the  nasal cavity of all  species.   Hyperplasla
1n the trachea was  also  observed  1n all species at 4.9 ppm, with more severe
hyperplastlc  effects  1n  rats  than  In .hamsters  or  rabbits.   H1stolog1cal
changes  In  the lungs and  bronchi  (hemorrhage  and peMvascular  and alveolar
edema) were observed In  rats and rabbits exposed  at  4.9 ppm.  These effects
were not observed  In hamsters.  At  1.4 ppm  acroleln,  squamous metaplasia and
neutrophll  Infiltration of the nasal mucosa  of  rats were observed.
    As  Indicated  by  the  studies  of  Lyon  et   al.  (1970)  and  Feron  et  al.
(1978), rabbits and hamsters seem to  be less sensitive to Inhaled acroleln.
Rats  seem  to  be  Intermediate  In  their response  to  Inhaled  acroleln,  with
dogs and monkeys being  the most sensitive.
    A  study  reported  by  Costa  et al.  (1986)  and  Kutzman  et  al.  (1985)
further  Investigated  the response  of  rats  to  Inhaled  acroleln.   Groups  of
male  and  female   Fischer  344  rats  (number  unspecified)  were  exposed  to
filtered air  0.4,   1.4 or  4.0 ppm  (0.9,  3.2 or  9.2  mg/m3)  acroleln  for  62


0103h                               -7-                              10/23/86

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days  (6  hours/day,  5 days/week).  Endpolnts  were  assessed 6 days  after  the
final  exposure  to  emphasize  the chronic  rather than  the acute effects  of
repeated  exposure  to  acroleln.   Parameters  examined  were  lung  function
(Costa  et  al.,  1986),  animal  weights,  organ-to-body  weight  ratios,  lung
composition and hlstologlcal changes  1n the lungs (Kutzman et al., 1985).
    In rats exposed at  4.0  ppm, a  substantial  decrement  In lung function  was
observed.   Expiratory  flow  rates  were  decreased  and   lung  volumes were
enlarged, suggesting  the presence of  obstructive  lesions  1n both  small  and
large  airways.    Rats  exposed  at  0.4  ppm  acroleln  showed  "supernormal"
maximal air flows.   Parenchymal  tissue density of the  lungs  was  found to be
significantly Increased  (+15%)  In this  group,  but  was  not affected  at  the
higher  exposure  concentrations.    Costa  et  al.   (1986)  stated  that  the
Increase  In air  flow and  tissue  density at  0.4 ppm  provided  evidence  of
parenchymal  restriction.   The  authors  concluded  that  under  the  exposure
conditions  used  In  the  study,  acroleln  produced  contradictory  functional
lesions  at  the 4.0  ppm  and  0.4 ppm  exposure  levels.   These effects were
essentially cancelled In the 1.4 ppm exposed group.
    Other  effects of  acroleln  exposure were  reported  by  Kutzman   et  al.
(1985).   At 4.0  ppm,  32/57  male rats  died  while none  of  the  8  exposed
females died.  The average  weights of  the  4.0 ppm exposed rats were signifi-
cantly less than controls,  while weights of  the  1.4 and 0.4 ppm exposed rats
did not  differ  from controls.  Organ-to-body weight ratios  were  measured In
8 male  rats from each  exposure group.   The ratios of all  organs except  the
liver  and  spleen were  significantly  greater  (p<0.05)  In  the 4.0 ppm rats
than  \r\  the other   groups.   The  greatest  Increase  was  observed   1n  the
lung-to-body weight ratio.
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  ,  Cellular  contents  of  lungs  from male  rats  exposed to 4.0  ppm acroleln
varied  from  control  values;  DNA  was  117% of  the  control  value,  protein.
120%, elastln,  174% and collagen,  137%.  Except  for  an Increase In collagen
In  rats  exposed at  1.4  ppm  (113%  of control value),  the  composition  of the
lungs of rats exposed at 0.4 and 1.4 ppm were similar to controls.
    H1stolog1cal examination of  lungs  from rats  found  dead or  moribund that
were  exposed  at 4.0 ppm  showed  severe  acute  bronchopneumonla  (Kutzman  et
al.,  1985).   Focal  alveolor  edema  with  sloughed cells  In  the  bronchi  and
bronchioles was observed; many  airways  were  plugged.  Tracheal  edema with
erosion  of  the mucosal  epithelium was also  observed  1n  these  rats.   Lungs
from  the 4.0  ppm  acroleln-exposed  survivors  showed  bronchlolar  epithelial
necrosis and  sloughing,  bronchlolar mucopurulent  plugs with  macrophages and
focal pneumonltls;  edema  1n  the  trachea and  perlbronchlal  lymph  nodes  was
also  observed.   Bronchlolar epithelial  necrosis  and  sloughed cells  1n  the
lumen were  observed  In  3 of the 31  1.4 ppm rats examined, as were Increased
numbers  of  alveolar  macrophages and enhanced  type II  cell hyperplasla.   No
pulmonary  lesions  attributable  to  acroleln  were observed  1n  the 0.4  ppm
exposure group.
    Bouley  et al.  (1975,  1976)  studied  the  effect  of  acroleln  exposure  on
the susceptibility  of  rats to  Samonella  enteritis.   In this  study,  110 SPF
OFA male rats were continuously exposed  to acroleln  vapor at 0.55 ppm (1.26
mg/m3) for  up to  77 days.  A  control  group of 110 rats was  Included  In the
study.  After 60 days of  exposure,  the mean body weights of acroleln-exposed
rats were -80%  of  controls.  Lung-to-body weight ratios were  similar between
exposed  and  control  rats  sacrificed  at  15 and  32 days, but were  higher  In
rats after 77 days of exposure.
0103h                               -9-                              10/23/86

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 '   Rats challenged  with  an L05Q  of  airborne Salmonella enteritis  showed  a
significantly Increased susceptibility  on  day 18 but not on  day  24.   At  day
18, 15/16  exposed  rats  died compared with 8/15  controls  (p<0.05).   After 63
days  of exposure,  death  rates  as  a  result  of  Salmonella  Infection  were
similar In both exposed and control  rats  (10/10),  Indicating  to the Investi-
gators that an adaptation phenomenon! had occurred after  ~3 weeks of exposure.
3.2.   CHRONIC
3.2.1.   Oral.  Data  regarding the toxldty  of  chronic  exposure  to acroleln
are very limited.  In  an unpublished  study,   L1j1nsky (n.d.)  gave acroleln to
rats  In a  limited  amount  of drinking water  at  100,  250 or 625  ppm,  5 days/
week  for up  to  2  years.  Mortality of  the rats  was  not  affected by acroleln
treatment;   because  carclnogenlclty  was  the only  other endpolnt  examined,
details of  this study will be presented In Section 4.2.1.
3.2.2.   Inhalation.   The  only   chronic  Inhalation  study  available  was
conducted  by  Feron  and  Kruysse  (1977), -who exposed 18  male and  18  female
Syrian  golden hamsters  to  4 ppm  (9.2 mg/m3)  acroleln  for  7  hours/day,  5
days/week  for 52 weeks.   Similar  groups of  control  hamsters  were exposed to
filtered air.  During the exposure period, hamsters  were weighed monthly  and
observed for  toxic signs.  After 52  weeks  of exposure,  3 males  and 3 females
were  killed.  The  surviving hamsters were observed  until week  81  when they
were  sacrificed.   Hematological  and  blood  biochemical  determinations  were
conducted  on  all   hamsters.   At  necropsy,  organ weights  were   recorded  and
organs were fixed for hlstopathologlcal examination.
    Hamsters  exposed   to   acoleln  experienced  . eye  Irritation,  excessive
salivation  and  nasal  discharge  during  the  first week of the study.   As  the
exposure  continued,  these  signs   were  no  longer  observed.    During  the
exposure period, the  average  body  weights of exposed males  and females were


0103h                               -10-                             10/23/86

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lower  than those  of  the  controls;  these  differences  decreased  during  the
postexposure  period.    A  statistically  significant  Increase  In  hemoglobin
content  and packed  cell  volume  was  observed  1n  acroleln-exposed  females.
The  remaining  hematologlcal  and  blood  biochemical  parameters  were  not
affected.
    The  only  statistically significant  organ weight differences  were found
In  female  hamsters;  liver weights were  slightly decreased and lung weights
were Increased.   The  only h1stopatho1og1cal  changes attributable to acrolein
exposure were  found  1n  the nasal cavity, where  a moderate degree of Inflam-
mation  and epithelial metaplasia  was  observed.   About  20%  of  the  hamsters
killed  at  week 81  still  showed  effects of  acrolein  exposure  1n  the nasal
cavity as  Indicated by thickened mucosa and exudation 1n the  lumen.
3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1.    Oral.    Pertinent  data  regarding   the  teratogenlc   effects   of
acrolein  following oral   exposure  could not be  located  In  the  available
literature.
3.3.2.    Inhalation.  As  part of  a  subchronlc  Inhalation study, Bouley  et
al. (1976)  examined  the reproduction of rats exposed  to  acrolein.  Hale and
female  SPF OFA  rats  were exposed  continuously  to 0.55  ppm  {1.26  mg/m3)
acrolein  vapor for  26  days.   Mating was  Initiated  on   the  fourth  day  of
exposure and females were examined 22  days  after Initiation of cohabitation.
No  significant difference was noted  1n the number of  pregnant rats,  the
number  of  fetuses  or  the mean weights of the fetuses.  No further data were
presented.
3.4.   TOXICANT INTERACTIONS
    Kane and  Alarle  (1978) studied  the  effects of  simultaneous  exposure  to
formaldehyde and  acrolein.  Groups  of  four Swiss-Webster  mice were exposed


0103h                               -11-                             01/13/87

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ta  varying  concentrations  of  acroleln,  formaldehyde alone  or  the  two  In
combination.   Respiratory  rates,  which  decrease with  greater  Irritation,
were measured as an Index of sensory  Irritation.   Eleven  I0-m1nute  exposures
were conducted In which the acroleln  concentration ranged  from  0.12-8.97  ppm
(0.28-20.6  mg/m3)  and the  formaldehyde  concentration ranged from  0.33-9.73
ppm  (0.41-11.95  mg/m3).   Data  from  these  exposures were  used In a  mathe-
matical model  that describes the  Interaction of  agents  acting at a  single
sensory receptor  site.   From the results,  Kane  and  AlaMe  (1978)  concluded
that acroleln  and formaldehyde  act  1n competitive  antagonism  for the  same
receptor sites when causing sensory Irritation.
    In  a  another  study  examining   the  Interaction  of  formaldehyde  with
acroleln, Babluk et al. (1985) exposed male  Fischer  344  rats to formaldehyde
at  15  ppm  (18 mg/m3).  6 hours/day  for  9  days,  and then  on  the  tenth  day
challenged  the rats with  acroleln vapor.  Sensory Irritation was  determined
by measuring  the respiratory rate depression during  exposure.   A depression
In respiratory rate Is a  protective defense  against  respiratory Irritants;  a
lower respiratory rate allows less chemical  Into  the  lower respiratory tract.
    The  results   of   this  study  (Babluk  et  al.,  1985)   Indicated  that  1n
nonpretreated  rats,  6.0  ppm  (13.8  mg/m3)  acroleln  was  the  RD«-n-    I"
formaldehyde  pretreated   rats,   29.6  ppm  (67.9   mg/m3)   acroleln,  a  5-fold
Increase, was required to reach the R05Q-
    In  a  chronic  Inhalation  study,  Feron  and Kruysse  (1977)   examined  the
effect  of  acroleln   on   the  Cc'rdnogenlc  potential  of  benzo(a)pyrene  and
dlethylnltrosamlne.   Hamsters exposed to acroleln vapor  at 4  ppm  (9 mg/m3)
for 52  weeks  and to weekly  In^.ratracheal Instillations of  benzo(a)pyrene or
weekly  Injections  of  d1ethylr»1trosam1ne  did  not  show Increased  tumor  Inci-
dences.   Acroleln  did appear to  shorten  the t1me-to-tumor  1n  the  benzo(a)-
pyrene-dosed group.

0103h                               -12-                             10/23/86

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                              4.   CARCINOGENICITY
4.1.   HUMAN DATA
    Pertinent  data  regarding  the  carcinogenic  potential  of  acroleln  In
humans  following  oral  or  Inhalation  exposure  could not  be located  In  the
available literature.
4.2.   BIOASSAYS
4.2.1.   Oral.  The  only  animal  study available concerning  the  carcinogenic
potency  of  acroleln  by the  oral  route was an  unpublished  study  by Lljlnsky
(n.d.).   In  this  study, groups of  20 male Fisher 344  rats, caged  In groups
of  4,  were  provided  with  80  ml  drinking  water/cage,  which  contained
acroleln  at  100,  250  or  625 ppm,  5 days/week  for  120,  120 and  100 weeks,
respectively.  On  the  remaining  2 days each  week,  rats were provided  with
tap water  ad.  libitum,  because 1n  the  previous 5  days  access   to  drinking
water  containing  acroleln  was limited  to  less   than expected consumption  to
Insure  1ngest1on  of  the full dose of acroleln.   A  group of 20  female  rats
were  treated In  a  similar  manner  with water  containing 625 ppm  acroleln.
Whether  female rats  were  treated  at  the lower  doses 1s unclear.   The manner
of  treatment of  the control group  of 20  male and 20 female  rats  was  not
specified  1n the  paper.   At  the  end  of  the   treatment  period,  rats  were
allowed  to  die  naturally,  and survivors were sacrificed at 130  weeks.   All
rats were necropsled and all major organs were examined hUtoToglcally.
    The  only significant  result  was an  Increase 1n  the Incidence  of  rare
adrenal  cortex  adenomas  In  female  rats  treated  at  625  ppm (5/20  treated,
0/20  controls;  p=0.02).  At  the  NCI -  Frederick  Cancer  Research  Facility,
where  this  study  was completed,  the  historical Incidence of this  tumor  was
12/263 (4.6X) 1n untreated or "solvenf'-treated females.
4.2.2.   Inhalation.    In  the  chronic  Inhalation  study  conducted  by  Feron
and  Kruysse  (1977)   (see  Section  3.2.2.),   no  statistically   significant

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U.S. EPA.   1980b.   Hazard  Profile for Chloroethane.  Prepared by  the  Office
of   Health   and   Environmental   Assessment,   Environmental   Criteria   and
Assessment Office, Cincinnati, OH for the Office  of  Solid  Waste,  Washington,
DC.

U.S. EPA.   1980c.   Guidelines  and Methodology  Used 1n  the  Preparation  of
Health  Effect   Assessment  Chapters  of  the  Consent Decree  Water  CrHerl-a
Documents.  Federal Register.   45(231):  49347-49357.

U.S. EPA.   1983.   Methodology and Guidelines for  Reportable  Quantity  Deter-
minations Based on  Chronic Toxldty  Data.   Prepared by the Office of  Health
and  Environmental  Assessment,  Environmental Criteria and  Assessment  Office,
Cincinnati,   OH  for  the   Office  of  Solid  Waste- and  Emergency  Response,
Washington,  DC.

U.S. EPA.   1986a.  Summary Review  of Health  Effects  Associated  with  Mono-
chloroethane:  Health  Issue Assessment.  Internal  Review Draft.  Prepared  by
the  Office  of   Health  and Environmental  Assessment, Environmental  Criteria
and Assessment  Office.  Research Triangle Park,  HC.

U.S.  EPA.   1986b.   Health   and  Environmental   Effect  Profile   for  Methyl
Chloride.   Prepared  by the  Office of  Health and  Environmental  Assessment,
Environmental  Criteria  and Assessment Office, Cincinnati, OH for  the  Office
of Solid Waste and Emergency  Response, Washington, DC.

U.S.  EPA.   1986c.   Guidelines   for  Carcinogen   Risk  Assessment.   Federal
Register.  51(185): 33992-34003.


0087h                               -14-                             08/05/87

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dose-related  response for  acroleln  In  S^. typhlmurlum  strain  TA104, a  new
strain  designed  to  detect  peroxides   and  other  oxldants.   Hales  (1982)
reported  that acroleln  was  nonmutagenlc  In  S^. typhlmurlum strain  TA1535.
Haworth  et  al.  (1983)  found  that  acroleln was  negative In £^  typhlmurlum
strains  TA1535.  TA1537,  TA98  and  TA100 with  S-9 metabolic  activation  from
both rat and hamster  livers.
    Acroleln  was  not  mutagenlc  1n  Escherlchla  coll  strain  K12/343/113
(Ellenberger  and  Mohn,  1977).  Hemm1nk1 et  al.   (1980)  reported  acroleln  to
be weakly mutagenlc In £_._ coll strain WP2 uvr A (trp~).
    Acroleln  has  been   tested  for  the  Induction of  sex-linked  recessive
lethals  In  Drosophlla.    In a  study  by Rapaport (1948), DrosophUa  larvae
were allowed  to  feed  on  nutrient medium containing acroleln.   The concentra-
tion of  acroleln  was  not reported, but  the  level used was  reported to cause
death  In >75% of the treated larvae.   The  Incidence  of sex-linked recessive
lethals  In survivors  of acroleln treatment was 2.23%,  compared  with 0.19% In
controls.  When adult male  Drosphlla were  fed  a  5X sucrose solution contain-
ing 3000 ppm acroleln or were  Injected with acroleln at 200 ppm In  saline,
however, the  Incidence of recessive  lethals  In treated flies  was  essentially
Identical to controls (ZlmmeMng et al., 1985).
    Au  et  al.  (1980)  tested  acroleln for  sister  chromatld  exchange  and
chromosome  breaks In  Chinese  hamster  ovary  cells.   The  results showed  a
dose-related  response for  sister  chromatld exchange  without S-9, but  were
negative with S-9  metabolic  activation.    Tests for  chromosome breaks  In
Chinese  hamster  ovary cells  were  confounded  by  toxldty,  but the  Investi-
gators  concluded  that   the  response   was   not   a  true  Indication  of  the
mutagenlc effects of acroleln (Au et al., 1980).
0103h                               -15-                             01/13/87

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    Epstein et al. (1972) studied acroleln  In a  dominant  lethal  assay.   Male
8- to 10-week-old ICR mice received single  1ntraper1toneal  Injections of 1.5
or 2.2 mg/kg acroleln and were mated with  three  untreated  females/week  for  8
weeks.   The  authors  stated  that  the  Incidence  of  early  fetal  deaths  and
prelmplantatlon losses were within control  limits.
4.4.   ' HEIGHT OF EVIDENCE
    The  Increased  Incidence  of  adrenal  cortex  adenomas  In  female   rats
treated at 625 ppm In drinking water provides limited  evidence that acroleln
may  be  carcinogenic   to  animals.   Results  of  mutagenldty  tests   are  equi-
vocal; In  some  tests acroleln has not  been mutagenlc, while  1n other  tests
1t has been shown to  be  weakly mutagenlc.   Structural  activity relationships
also  suggest  possible carcinogenic activity of acroleln.
    There are no  ep1dem1olog1cal  studies relating acroleln exposure  to car-
dnogenlclty  In the  present  data base.  The  skin painting and  subcutaneous
studies of acroleln are  Inadequate to assess carcinogenic  potential;  similar
studies of Its  metabolite  glycldaldehyde are,  however, supportive  of a car-
cinogenic potential.   There are two different families of  chemical  compounds
that   may  be  functionally  related  to  acroleln:    aldehydes  and dlenes.   The
first group  Include  chemicals such as  formaldehyde and acetaldehyde,  which
are considered to be  probable human carcinogens  by  the U.S.  EPA.   The second
group Includes  dlene-vlnyl  compounds  such as ethylene oxide,  acrylonltrlle,
vinyl chloride and 1,3-butadlene.  These have been classified  as probable or
known (vinyl  chloride) human carcinogens.
    Based  upon  1) the structural relationship  between acroleln and  related
compounds  that  are  potentially  carcinogenic  to  humans,  2)  animal  studies
that   suggest  a  carcinogenic potential  for a known  metabolite of  acroleln,
and  3)  the lack  of   ep1dem1olog1cal  data, acroleln  1s   considered  to  have


0103h                               -16-                             03/11/87

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"limited"  animal  evidence  for  carclnogenlclty  (U.S.  EPA,  1986a).   Because
the  evidence  In animals  1s limited, acroleln  should be  classified  1n  IARC
Group  3;  that  1s,   1t  cannot  be  classified  as   to  Its  carclnogenlclty.
According  to  the  U.S.  EPA classification scheme  (U.S.  EPA,  1986b),  acroleln
may be classified In Group C, limited animal evidence of carclnogenlclty.
0103h                               -17-                             08/03/87

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                     5.  REGULATORY STANDARDS AND CRITERIA

    In developing an ambient  water quality criteria  for acroleln, the  U.S.
EPA (1980a)  derived  an RfD of 1.56xlO~2  mg/kg/day,  or  1.09 mg/day for  a  70
kg human.  This RfD  was derived from  the  study  by  Newell (1958),  In which  no
effects  were  observed  In  rats  provided  with  drinking  water   containing
acroleln at  200 mg/t  for 90  days.   A  rat  body  weight of  450  g, a  water
consumption  of  35  ml/day  and an  uncertainty   factor  of 1000  were used  to
calculate  this  RfD   (U.S.  EPA,  1980a).    Assuming  a  70  kg  human   drinks  2 i
of water/day  and  eats 6.5  g  of fish/day  with  a bloconcentratlon  factor  of
215,   a  water quality  criteria  for acroleln  of 0.32 mg/l  was derived  from
the RfD of 1.56xlO~* mg/kg/day (U.S.  EPA,  1980a).
    The RfD  of  1.56xlO~a  mg/kg/day was also  presented  In  U.S. EPA (1985a),
and rounded to 1.6xlO~a mg/kg/day  In  U.S.  EPA  (1985a).
    The  ACGIH (1986)  TLV-THA for  acroleln  1s  0.1  ppm (-0.25 mg/m3);  the
TLV-STEL  1s  0.3 ppm (-6.8 mg/m3).   ACGIH  (1986)  stated  that  the  TWA-TLV
Is sufficiently low  to minimize but not to prevent  Irritation to  all  exposed
Individuals.  The OSHA (1985)  PEL  Is  also  0.1  ppm.
0103h                               -18-                             08/03/87

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                              6.   RISK  ASSESSMENT
6.1.   SUBCHRONIC REFERENCE DOSE (RfD$)
6.1.1.   Oral  (RfDgJ.   The  unpublished  study  by  Lljlnsky  (n.d.)  showed
an  Increased  Incidence of  adrenal  cortex adenomas  1n female rats  provided
with  acroleln  1n their drinking  water.  Since a q  *  was not calculated  at
this  time  because  of Inadequate  data,  but  concern over  the  carclnogenlclty
of acroleln exists, an RfDSQ value will not be derived.
6.1.2.   Inhalation  (RfDSI).   Limited  evidence  Indicates that  acroleln  Is
an oral carcinogen; therefore, an RfOSI value will not be derived.
6.2.   REFERENCE DOSE (RfD)
6.2.1.   Oral  (RfDQ).   Because the  above stated  concerns also  apply  to  an
RfD, an RfDQ value will not be calculated for acroleln.
6.2.2.   Inhalation  (RfD.).  Limited  evidence  Indicates that  acroleln  Is
an oral carcinogen; therefore, an RfD, value will not be derived.
6.3.   CARCINOGENIC POTENCY (q^)
6.3.1.   Oral.  The  study  by  Lljlnsky (n.d.) provides  limited evidence that
acroleln may  be carcinogenic  following  oral  exposure.   In  this  study,  an
Increase 1n the  Incidence  of adrenal  cortex  adenomas  was  observed  Vn treated
female rats  (5/20  treated, 0/20  control).  The  treated  females,  four  rats/
cage, were  provided  with  80 ml  drinking water/cage/day  which contained  625
ppm  acroleln,  5 days/week  for 100  weeks.   The  remaining 2 days/week,  the
rats were  provided with  tap water ad  libitum.  The  rats  were allowed to die
naturally,   with  survivors  sacrificed  at 130  weeks.   The  treatment of  the
control group  of 20  female rats,  particularly  with  regard to  limited access
to drinking water,  was not specified.
0103h                               -19-                             08/03/87

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    The  Increased  Incidence of adrenal  cortical  adenomas In  treated  female
rats  cannot  be used  to derive a  q * for  oral  exposure.  Adenomas  without
other  "tumor"   Incidences   are  considered  to  be   Inadequate  data  for  q *
derivation.
6.3.2.   Inhalation.  The only  chronic Inhalation  study  of  acroleln  (Feron
and Kruysse, 1977)  did  not show  an Inceased tumor  Incidence;  therefore,  an
Inhalation q *  cannot be calculated.
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                                7.  REFERENCES

ACIGH  (American Conference  of Governmental  Industrial  Hyglenlsts).   1986.
Documentation  of  Threshold  Limit  Values and  Biological  Exposure  Indldes,
5th ed.  Cincinnati, OH.  p. 11.

Albln, T.B.   1962.   Handling and  toxicology.  .In: Acroleln, C.W.  Smith,  Ed.
John Wiley and Sons, Inc., New York.  p. 234.  (Cited In  U.S.  EPA,  1980a)

Au, W.,  O.Z.  Sokova, B.  Kopln and F.E. Arrlghl.  1980.  Cytogenlc  toxlclty
of  cyclophosphamlde and  Us  metabolites jjn  vitro.   Cytogenet. Cell  Genet.
26: 108-116.

Babluk,  C.,   U.H.  Stelnhagen  and  C.S.  Barrow.   1985.   Sensory  Irritation
response  to  Inhaled aldehydes  after  formaldehyde  pretreatment.    Toxlcol.
Appl. Pharmacol.  79(1): 143-149.

Beauchamp, R.D.,  Jr.,  D.A.  Andjelkovlch,  A.D.  Kllgerman,  K.T.  Morgan,  H.D.
Heck.  1985.  A critical  review of  the  literature on acroleln  toxlclty.   CRC
Crlt. Rev. Toxlcol.  14(4): 309-380.

Bouley, G., A. Oubreull,  J.  Godln  and C.  Boudene.  1975.  Effects  of a small
dose of acroleln constantly  Inhaled by  rats.  Eur. J.  Toxlcol.  Environ.  Hyg.
8: 291-297.  (Cited 1n U.S. EPA, 1986a)

Bouley.  G.,   A.  Oubreull,   J.  Godln,  M.   Bolsset   and  C.   Boudene.   1976.
Phenomena of  adaption  In rats continuously  exposed  to low concentration  of
acroleln.  Ann. Occup.  Hyg.  19(1): 27-32.

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Brabec, M.J.  1982.  Aldehydes and acelates.  in:  Patty's  Industrial  Hygiene
and Toxicology,  Vol.  2A,  3rd ed., G.D.  Clayton and R.E. Clayton,  Ed.   John
Wiley and Sons,  Inc.,  New York.   p.  2266, 2634-2637,  2648-2656.

Carson, B.L.,  C.M.  Beall, H.V.  Ellis,   L.H.  Baker  and B.L. Herndon.   1981.
Acroleln Health Effects.  EPA 460/3-81-034.   NTIS PB82-161282.

Costa, D.L., R.S. Kutzman,  J.R.  Lehmann  and R.T. Drew.   1986.   Altered lung
function  and  structure In  the   rat  after  subchronlc  exposure   to  acroleln.
Am. Rev. Resplr. D1s.   133(2):  286-291.

Oramlnskl, U.,  E.  Eder and  D. Henschler.   1983.  A new pathway  of acroleln
metabolism 1n rats.   Arch. Toxlcol.   52:  243.

Egle,  J.L.,  Jr.  1972.   Retention  of Inhaled  formaldehyde,  proplonaldehye,
and acroleln 1n the dog.  Arch.  Environ.  Health.  25:  119-124.

Ellenberger, J.  and G.R.  Mohn.   1977.  Mutagenlc  activity  of  major  mammalian
metabolites of  cyclophosphamlde  toward  several  genes  of Escherlchla  cojl.
J. Toxlcol. Environ. Health.   3:  637-650.  (Cited In U.S.  EPA,  1986a)

Epstein,  S.S.,  E.  Arnold, J. Andrea, W. Bass and Y.  Bishop.   1972.   Detec-
tion of  chemical  mutagens by dominant lethal  assay In the mouse.   Toxlcol.
Appl. Pharmacol.  23:  288-325.

Feron, V.J. and A.  Kruysse.  1977.   Effects of  exposure to acroleln vapor In
hamsters  simultaneously treated  with  benzo(a)pyrene  or  dlethylnltrosamlne.
J. Toxlcol. Environ. Health.   3:  379-394.

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Feron, V.J., A.  Kruyssee,  H.P.  Til  and  H.R.  Immel.   1978.   Repeated  exposure
'  »
to  acroleln   vapor.    Subacute   studies   In   hamsters,   rats   and   rabbits.
Toxicology.  9: 47-57.

Hales,  B.   1982.   Comparison  of  the  mutagenldty and  teratogenldty  of
cyclophosphamlde  and   Its   active   metabolites,   4-hydroxycyclophosphamlde,
phosphoramlde mustard, and acroleln.  Cancer.  Res.   42:  3016-3021.

Hansch,   C.   and  A.J.   Leo.   1985.   Medchem  Project.    Pomona   College,
Claremont, CA.

Haworth,  S.,  T.  Low!or,  K.  Mortelmans,  W.  Speck  and  E.  Zelger.   1983.
Salmonella mutagenldty  test results  for  250 chemicals.  Environ.  Hutagen.
1: 3-142.

Hemmlnkl, K., K. Falck and H.  Va1n1o.   1980.   Comparison  of  alkylatlng  rates
and  mutagenldty  of  direct  acting   Industrial  and  laboratory  chemicals.
Arch.  Toxlcol.  46:  277-285.

Kane,   I.E.  and  Y.  Alarle.   1978.   Evaluation  of  sensory  Irritation  from
acroleln-formaldehyde mixtures.  Am.   Ind.   Hyg.  Assoc.  J.   39:   270-274.
(Cited In U.S. EPA,  1986a)

Kutzman,  R.S., E.A. Popenoe,  M.  Schmaeler  and R.T.  Drew.  1985.  Changes  In
rat lung  structure and  composition as  a  result  of subchronlc exposure  to
acroleln.  Toxicology.  34(2): 139-151.
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LlJInsky,  W.   n.d.   Chronic  studies   In  rodents   of   vinyl   acetate   and
compounds related  to  acroleln.   Unpublished.  NCI-Freder1ck Cancer  Research
Facility, Frederick, MD.

LlJInsky, W.  and A.M. Andrews.   1980.   Mutagenldty of  vinyl  compounds  In
Salmonella typhlmurlum.  Teratogen.  Carcinogen.  Mutagen.   1:  259-267.

Lutz,  0.,  E.  Eder,   T.  Neudecker  and  0.  Henschler.    1982.    Structure-
mutagenldty  relationships 1n 2,8-unsaturated carbonyllc  compounds and  their
corresponding allyllc alcohols.   Mutat.  Res.   93:  303-315.

Lyon, J.P.,  L.J. 'Jenrlng, Jr.,  R.A.  Jones,  R.A.  Coon and J. Slegel.   1970.
Repeated  and   continuous   exposure  of  laboratory  animals  to  acroleln.
Toxlcol. Appl. Pharmacol.   17: 726-736.

Marnett, L.J., H.K. Hurd, M.C. Hollsteln,  D.E. Levin, H.  Esterbaure  and  8.N.
Ames.   1985.   Naturally  occurring  carbonyl   compounds   are  mutagenlc   In
Salmonella  tester  strain  TA104.  Mutat.  Res.   148:  25-34.   (Cited  In  U.S.
EPA. 1986a)

NAS (National Acacemy of Sciences).  1977.   Drinking  Water and Human Health.
Washington,  DC.

Newell,   G.W.    19118.   Acute  and  Subacute  Toxldty  of  Acroleln.   Stanford
Research Institute.  SRI  Project No. 5-868-2.  (Cited  In  NAS, 1977)
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OSHA  (Occupational  Safety and  Health  Administration).   1985.   Safety  and
Health Standards.  Code of Federal Regulations.  29: 1910.1000.

Rapaport.  I.A.   1948.   Mutations  Induced  by unsaturated  aldehydes.   Ookl.
Akad. Nauk. USSR   61: 713-715.  (Rus.)   (Cited In U.S. EPA, 1986a)

Salamon,  M.H.  and F.J.  C. Roe.   1956.   Further tests  for  tumor Initiating
activity:  N,  N-01-(2 chloroethyl)-p-am1nopheny1-butyr1c  acid  (CB 1348) as an
Initiator  of  skin  tumor  formation   In  the  mouse.   Br.  J.   Cancer.   10:
363-378.   (Cited In  U.S.  EPA, 1986a)

Stelner,  P.E., R.  Steele  and  F.C.  Koch.   1943.  The possible cardnogenlcHy
of  overcooked meats,  heated cholesteral,  acroleln  and heated  sesame  oil.
Cancer Res.  3: 100-107.   (Cited 1n U.S. EPA, 1986a)

U.S.  EPA.  1980a.   Ambient  Water  Quality  Criteria Document  for Acroleln.
Prepared  by the Office  of Health  and  Environmental  Assessment, Environmental
Criteria  and Assessment Office, Cincinnati,  OH for  the Office of Hater Regu-
lations and Standards, Washington, DC.  EPA 440/5-80-016.  NTIS PB81-117277.

U.S.  EPA.  1980b.   Guidelines  and Methodology  Used  1n the  Preparation  of
Health  Effect Assessment Chapters  of  the  Consent  Decree  Water  Criteria
Documents.  Federal Register.  45(231): 49347-49357.
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                              M.S.
                              Region 5, Library (PI-12J)
                              77 West jacteon Boulevard, 12th
                                       t 60604-3590

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, ,U.S.  EPA.   1983.   Methodology and Guidelines for Reportable  Quantity  Deter-
  minations Based on  Chronic  Tox1c1ty  Data.   Prepared by the Office  of  Health
  and  Environmental  Assessment,  Environmental  Criteria and  Assessment  Office,
  Cincinnati,  OH  for  the  Office  of  Solid  Waste  and  Emergency  Response,
  Washington, DC.

  U.S.  EPA.   1985a.  Health  and Environmental Effects  Profile for  Acroleln.
  Prepared by the Office of Health  and  Environmental  Assessment,  Environmental
  Criteria and Assessment Office, Cincinnati, OH for  the  Office of  Solid Waste
  and Emergency Response, Washington,  DC.

  U.S.  EPA.   1985b.  Reference  Values  for Risk Assessment.   Prepared  by  the
  Office  of  Health  and  Environmental  Assessment,  Environmental  Criteria  and
  Assessment Office, Cincinnati, OK for the Office  of  Solid  Waste,  Washington,
  DC.

  U.S. EPA.  1986a.  Health Assessment Document for Acroleln.   Prepared  by  the
  Office  of  Health  and  Environmental  Assessment,  Environmental  Criteria  and
  Assessment Office, Research  Triangle  Park,  NC for the  Office of  A1r  Quality
  Planning and Standards. Washington,  OC.   EPA 600/8-86-014A.

  U.S.  EPA.    1986b.   Guidelines   for  Carcinogen  Risk  Assessment.    Federal
  Register.  51(185): 33992-34003.

  ZlmmeMng, S.,  J.H.  Mason,  R. Valencia  and  R.C.  Woodruff.   1985.   Chemical
  mutagenesls testing In DrosophHa.  II.  Results of  20  coded  compounds  tested
  for the National Toxicology  Program.   Environ. Mutagen.   7(1): 87-100.


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                                            EPA/600/8-88/013
                                            July,  1987
          HEALTH EFFECTS ASSESSMENT
                 FOR  ACROLEIN
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
      OFFICE OF  RESEARCH AND DEVELOPMENT
    U.S. ENVIRONMENTAL PROTECTION AGENCY
            CINCINNATI, OH 45268

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                                   TECHNICAL RETORT DATA
                            (Htmt nud liutntctmiu on Ou revtnt be fort eomplttingl
 EPA/600/8-88/013
                                                           3. RECIPIENT'S ACCESSION NO.
                                                               PB88-179494
4. TITLE AND SUBTITLE

  Health Effects Assessment for Acrolein
                                                           S. REPORT DATE
                                                           •. PERFORMING ORGANIZATION CODE
7. AUTMOR(S)
                                                           •. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME AND AOORESS
                                                           10. PROGRAM ELEMENT NO.
                                                           11. CONTRACT/CHANT NO.
12. SPONSORING AGENCY NAME AND AOORESS
                                                           13. TYPE OF REPORT AND PERIOD COVERED
 Environmental  Criteria and Assessment Office
 Office of Research  and Development
 U.S. Environmental  Protection Agency
 Cincinnati. QH  45268	
                                                           14. SPONSORING AGENCY CODE

                                                              EPA/600/22
15. SUPPLEMENTARY NOTES
16. ABSTRACT
   This report  summarizes and evaluates  information relevant to a preliminary interim
 assessment of  adverse health effects associated with specific chemicals or compounds.
 The Office of  Emergency and Remedial Response (Superfund) uses these  documents in
 preparing cost-benefit analyses under Executive Order 12991 for decision-making under
 CERCLA.  All estimates of acceptable intakes  and carcinogenic potency presented in
 this document  should be considered as preliminary and reflect limited resources
 allocated to this project.  The intent  in  these assessments is to suggest acceptable
 exposure levels  whenever sufficient data are  available.  The interim  values presented
 reflect the relative degree of hazard associated with exposure or risk to the
 chemical(s) addressed.  Whenever possible,  two categories of values have been
 estimated for  systemic toxicants (toxicants for which cancer is not the endpoint of
 concern).  The first, RfD$ or subchronic reference dose, is an estimate of an exposure
 level that would not be expected to cause  adverse effects when exposure occurs during
 a limited time interval.  The RfD is an estimate of an exposure level  that would not
 be expected to cause adverse effects when  exposure occurs for a significant portion
 of the lifespan.  For compounds for which  there is sufficient evidence of
 carcinogenicity, qi*s have been computed,  if  appropriate, based on oral and
 inhalation data  if available.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                             b. IDENTIFIERS/OPEN ENDED TERMS  C.  COS AT I Field/Group
1«. DISTRIBUTION STATEMENT

  Public
                                              19. SECURITY CLASS (This Report!

                                                Unclassified
                                                                         21. NO. OF PAGES
                                              20. SECURITY CLASS
                                                Unclassified
                                                                        22. PRICE
EPA Pw» 2220.1 (»•». 4-77)   pRKvious COITION i> OMOLKTK
                                             U.S. Environmental Protection Agemry
                                             Region 5, Library (PL-12J)
                                             ft*? #ck^§?ule*>«i. 12th Floor
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